Bone Physiology And Calcium Homeostasis PDF

# Bone Physiology And Calcium Homeostasis ## Prepared By: - Dr. Abdullah K. Ghafour - 3rd year IBFMS trainee ## Supervised By: - Dr. Ali Abdunabi Alwan ## 20th September 2017 # Bone Composition And Structure - Bone is a highly specialized supporting framework of the body, characterized by its r...

# Bone Physiology And Calcium Homeostasis ## Prepared By: - Dr. Abdullah K. Ghafour - 3rd year IBFMS trainee ## Supervised By: - Dr. Ali Abdunabi Alwan ## 20th September 2017 # Bone Composition And Structure - Bone is a highly specialized supporting framework of the body, characterized by its rigidity, hardness, and power of regeneration and repair. - It protects the vital organs, provides an environment for marrow, acts as a mineral reservoir for calcium homeostasis and a reservoir of growth factors and cytokines, and also takes part in acid-base balance. - Bone constantly undergoes modeling (reshaping) during life to help it adapt to changing biomechanical forces, as well as remodeling to remove old, micro-damaged bone and replace it with new, mechanically stronger bone to help preserve bone strength. - Bone consists of a largely collagenous matrix which is impregnated with mineral salts and populated by cells - osteoclasts, osteoblasts and osteocytes. - Newly formed bone tissue, which is unmineralized, is called osteoid and is usually seen only where active new-bone formation is taking place this soon becomes mineralized, but the immature tissue is somewhat disorganized, with collagen fibers arranged haphazardly and cells having no specific orientation; in this state it is called woven bone - typically seen in the early stages of fracture healing. - The mature tissue is lamellar bone, in which the collagen fibers are arranged parallel to each other to form multiple layers (or laminae) with the osteocytes lying between the lamellae. - Lamellar bone exists in two structurally different forms: compact (cortical) bone and cancellous (trabecular) bone. - Compact bone is dense and strong and is found where support matters most, It is made up of compact units-haversian systems or osteons - Cancellous bone has a honeycomb appearance; it makes up the interior meshwork of all bones and is particularly well developed in the ends of the tubular bones and in the vertebral bodies. - Fully formed bones are covered (except at the articular ends) by a tough periosteal membrane, the deepest layer of which consists of potentially bone-forming cells. - Bone cells are of three types: osteoblasts, osteocytes and osteoclasts. - Osteoblasts are concerned with bone formation and osteoclast activation. They develop from mesenchymal precursors in the bone marrow and beneath the periosteum. - Differentiation is controlled by a number of interacting growth factors, including bone morphogenetic proteins (BMPs). Prompted by parathyroid hormone (PTH) PTH), osteoblasts also play an important role in the initiation and control of osteoclastic activity. - At the end of each bone-forming cycle, the osteoblasts either remain on the newly formed bone surface as quiescent lining cells or they become embedded in the matrix as 'resting' osteocytes. - Osteoclasts, considerably larger multi-nucleated cells, are the principal mediators of bone resorption. - They develop from precursors in the haemopoietic marrow under the influence of local osteoblastic stromal cells that generate an essential osteoclast differentiating factor which is required to initiate osteoclast maturation and bone resorption. - Almost one half the bone volume is mineral matter - mainly calcium and phosphate in the form of crystalline hydroxyapatite. - In mature bone the proportions of calcium and phosphate are constant and the molecule is firmly bound to collagen.. - While the collagenous component lends tensile strength to bone, the crystalline mineral enhances its ability to resist compression. - Bone consists of a largely collagenous matrix which is impregnated with mineral salts and populated by cells. - Type I collagen fibres, derived from tropocollagen molecules produced by osteoblasts, make up over 80% of the unmineralized matrix. - They form a network which embodies a mucopolysaccharide, ground substance and also acts as a scaffold on which the mineral component - crystalline hydroxyapatite - is deposited. - Other non-collagenous proteins exist in small amounts in the mineralized matrix-mainly sialoproteins (osteopontin), osteonectin, osteocalcin (bone Gla protein) and alkaline phosphatases. # Bone Development And Growth - Bones develop in two different ways: by ossification of a prior cartilage model (endochondral ossification) and by direct (intramembranous ossification). - Endochondral ossification is the usual manner in which tubular bones develop. - The actively growing physis consists of four distinct zones. Coextensive with the epiphysis is a zone of resting chondrocytes; this merges into a proliferative zone, multiplying by interstitial As these cells mature they constitute a hypertrophic zone which gradually becomes calcified; this zone of calcified cartilage undergoes osteoclastic resorption and finally, with the ingrowth of new blood vessels from the bony diaphysis ossification. - With the growth in length, the bone also has to increase in girth. In Intramembranous ossification new bone is added to the outside by direct ossification at the deepest layer of the periosteum where mesenchymal cells differentiate into osteoblasts (intramembranous, or 'appositional' bone formation); meanwhile 'old' bone is removed from the inside of the cylinder by osteoclastic endosteal resorption. - It also occurs as a response to periosteal stripping due to trauma, infection or tumour growth and in the the initial formation of the flat bones of the skull, mandible and clavicles. - REMODELING is the ongoing replacement of old bone tissue by new bone tissue. It takes place at different rates in various parts of body. - Osteoclasts are responsible for bone resorption (destruction of matrix). A delicate homeostasis exists between the actions of the osteoclasts in removing minerals and collagen and of osteoblasts in depositing them. - Bone remodeling cycle: ACTIVATION- osteoclasts are activated & begin secreting acids to resorb bone. RESORPTION- osteoclastic resoprtion occurs. REVERSAL- resorption stops & osteoblast take over. FORMATION- osteoblast form bone on the opposing surface to complete the bone reforming process. This cycle takes about 100 days in Compact bone & 200 days in Spongy bone. - Bone adjusts its strength in proportion to degree of bone stress. - The shape of the bone can be rearranged for proper support of mechanical forces in accordance with stress patterns. - New organic matrix is needed as the old organic matrix degenerates. - Wolff's Law: “Every change in the function of a bone is followed by certain definite changes in its internal architecture and its external conformation.” - Normal bone growth in the young and bone replacement in the adult depend on the presence of several minerals. - Sufficient amount of calcium and phosphorus (hydroxy apatite), must be included in the diet. - Magnesium deficiency inhibits the activity of osteoblasts. - Boron is a factor in bone growth. - Manganese deficiency inhibits laying down of new bone tissue. - Several vitamins like vitamins D, C, A, and B12, play a role in bone remodeling. - Vit C deficiency causes decrease collagen production, which retards bone growth and delays fracture healing. - Vit A helps to control the activity, distribution, and co-ordination of osteoblasts and osteoclasts during development. Its deficiency results in a decreased rate of growth in the skeleton. - Vit B12 may play a role in osteoblast activity. - Human growth hormone (HGH) is responsible for general growth of all body tissues, including bone. - Sex hormones (estrogens and testosterones) increase bone building activity of osteoblasts. - Insulin and thyroid hormones (T3, T4) promote normal bone growth and maturity. - Parathyroid hormone increases the number and activity of osteoclast, promotes recovery of Ca2+ from urine, and promotes formation of calcitriol. - Calcitonin (CT) inhibits activity of osteoclasts, speeds up Ca2+ absorption from blood, and accelerates Ca2+ deposit by bones. # Calcium Homeostasis - Total plasma [Ca++] = 2.5mmol/L. - Range is 2.1 to 2.6 mmol/L (8.8-10.4 mg/dL). - Very tightly controlled. - Only free, ionized Ca2+ is biologically active. - Changes in plasma protein concentration. - Increased [protein] → increased total (Ca2+). - Changes in anion concentration. - Increased [anion] → increased fraction of Ca2+ that is complexed → decrease ionized [Ca2+). - Acid base abnormality. - Preserving bone density. - Construction, formation and maintenance of bone and. - Homeostasis. - Nerve and muscle functions. - Increase in intracellular Ca2+ → Ca2+ binds to troponin C → moves tropomyosin out of the way → permitting the binding of actin to the myosin heads leading cross-bridge formation and the muscle contraction. - Neurotransmitter release. - Arrival of action potential to axonal terminal → opening of voltage gated calcium channels → calcium influx into the terminal → transmitter vesicle fuse with the release sites → release of transmitters into the cleft. - Calcium assists in maintaining all cells and connective tissues in the body and regulating mitotic transition and cell division. - Essential component in the production of enzyme and hormones that regulate digestion, energy, and fat metabolism. - Blood calcium is tightly regulated by: - Principle organ systems: - Intestine - Bone - Kidney - Hormones: - Parathyroid hormone (PTH) - Vitamin D - Calcitonin - PTH is secreted by chief cells of parathyroid glands. - It is the major factor of Ca2+ homeostasis in humans. - The dominant regulator of PTH is plasma Ca2+. - When Ca2+ falls, cAMP rises and PTH is secreted. - The overall action of PTH is to increase plasma Ca levels and decrease plasma phosphate levels. - Vitamin D: - Vitamin D is a lipid soluble. - Vitamin D increases Ca² absorption from the intestine and Ca2* resorption from the bone and decreases loss of calcium through the kidney by its active form 1,25,dihydroxycholecalciferol. - 1,25-(OH)2-D acts on osteoblasts which produce a paracrine signal that activates osteoclasts to resorb Ca** from the bone matrix. - 1,25-(OH)2-D also stimulates osteocytic osteolysis. - PTH also stimulates vitamin D synthesis. - Calcitonin: - Calcitonin is synthesized and secreted by the parafollicular cells of the thyroid gland. - The major stimulus of calcitonin secretion is a rise in plasma Ca2+ levels. - Calcitonin is a physiological antagonist to PTH with regard to Ca2+ homeostasis. - Calcitonin acts to decrease plasma Ca2+ levels. - Calcitonin inhibits activity of osteoclasts, resulting in decreased bone resorption (and decreased plasma Ca levels). # References - Linda S. Costanzo [2017] Physiology, 6th ed. by Elsevier, Inc. Richmond, Virginia, USA. - Solomon L., Warwick D., Nayagam S., [2010] Apley's System of Orthopaedics and Fractures, 9th ed. Hodder Arnold comp., London, UK. - Fogelman I., Gnanasegaran G., [2012] Radionuclide and Hybrid Bone Imaging, 1st ed. Springer-Verlag Berlin Heidelberg, Berlin, Germany. - John E. Hall Arthur C. Guyton, [2013] Textbook Of Medical Physiology, 13th ed. By Mosby, An Imprint of Elsevier, Tennessee, USA. - Khosla S1, Riggs BL. [2005] Pathophysiology Of Age-related Bone Loss And Osteoporosis, Endocrinol Metab Clin N Am 34 (2005) 1015-1030 # Thanks! - You can find this and all other my seminars at: https://www.slideshare.net/Abdulla1986/presentations